Cytochrome P450 Drug Interactions Within the HMG-CoA Reductase Inhibitor Class
- 1 January 2003
- journal article
- review article
- Published by Springer Science and Business Media LLC in Drug Safety
- Vol. 26 (1), 13-21
- https://doi.org/10.2165/00002018-200326010-00002
Abstract
The present review outlines the clinical relevance of pharmacokinetic drug interactions within the HMG-CoA reductase inhibitor class. These interactions can result in markedly increased or decreased plasma concentrations of some drugs within this class. However, the relationship between altered plasma concentrations and adverse effects or toxicity may not be linear. It is likely that other variables affect this concentration-effect relationship including: rapid changes in the concentration, concomitant lipid-lowering therapy or host genetic factors that code for different forms or amounts of metabolising enzymes and drug receptors. It is not currently possible to predict which patients will manifest clinically important drug-drug interactions, nor what concentration of an HMG-CoA reductase inhibitor will cause rhabdomyolysis. Thus, until prescribers have better scientific information from which to develop a ‘therapeutic range’ for each agent, caution should be exercised. In particular, patients taking a CYP3A4-metabolised agent, e.g. atorvastatin, simvastatin and lovastatin, should not be started on a CYP3A4 inhibitor or inducer without close monitoring.Keywords
This publication has 46 references indexed in Scilit:
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trialThe Lancet, 2002
- Safety and Tolerability of Pravastatin in Long-Term Clinical TrialsCirculation, 2002
- Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and SimvastatinAntimicrobial Agents and Chemotherapy, 2001
- Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomesBritish Journal of Clinical Pharmacology, 2001
- Concomitant use of cytochrome P450 3A4 inhibitors and simvastatinThe American Journal of Cardiology, 1999
- Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol LevelsNew England Journal of Medicine, 1998
- Metabolism and Drug Interactions of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors in Transplant Patients: Are the Statins Mechanistically Similar?Pharmacology & Therapeutics, 1998
- Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatinBritish Journal of Clinical Pharmacology, 1998
- EVALUATION OF FLUVASTATIN IN THE TREATMENT OF HYPERCHOLESTEROLEMIA IN RENAL TRANSPLANT RECIPIENTS TAKING CYCLOSPORINE1Transplantation, 1996
- Diltiazem myopathyAmerican Heart Journal, 1993